Friday October 26, 2012 0 comments
Detecting tiny changes in DNA gives researchers better tools to diagnose and treat disease
By Betsy Lynch
FORT COLLINS -- It's hard to fathom the full depth of information in the human genome. A mere 23 chromosomes to unravel doesn't sound daunting--until you consider that 22,000 individual genes and more than 6 billion bits of genetic code are represented in each human cell.
When something goes awry with our DNA, finding the anomaly is like looking for that proverbial needle in a haystack. It seems almost impossible--unless you have the right tools.
A small biotech company named KromaTiD is working to provide those tools. Researchers affiliated with Colorado State University and University of Texas Medical Branch-Galveston have been developing highly specialized "paints" to help scientists and diagnosticians spot nearly imperceptible changes in human DNA. Some of these changes may be linked to diseases and disabilities, such as cancer and autism.
Dr. Susan Bailey, Dr. Andrew Ray, Dr. Edwin Goodwin, Dr. Michael Cornforth and Dr. Joel Bedford founded KromaTiD in 2007. A common thread was they had all studied the effects of radiation exposure in people during stints at NASA and the Los Alamos National Laboratory. Each had a vested interest in devising practical ways to examine and quantify chromosomal changes, including inversions.
An inversion is a small segment of DNA that breaks off, flips around, and then rejoins the chromosome. Tiny inversions may be nearly impossible to see using traditional laboratory techniques and standard chromosome paints. The newer "chromatid" paints allow researchers to color a single side of a specific chromosome and then compare it to the opposite side.
Flourescent markers leave a signature at points of interest on the DNA strands. The technology was patented by CSU and UTMB-Galveston and the license granted to KromaTiD Inc.
Discovering and diagnosing
Dr. Chris Tompkins joined the company about two years ago to manage the business side of the business. Tompkins said KromaTiD's products and services break down into two basic classes: tools for discovering the genetic causes of diseases, and tools for diagnosing known genetic causes for diseases.
"Think of it as a process," he said. "You can use our tools to make a link between a certain mutation and a cancer or developmental disorder by finding those genetic markers. Then once those links are discovered, we then make very specific targeted assays for that mutation."
Business development consultant Cheryl Hite likens the technology to being able to go to a precise passage of recorded music as often as you want.
"Everyone's tape or genome is different," she said. She points to applications in "companion diagnostics" in which medical treatments -- such as cancer chemotherapies -- are tailored to an individual's personal biochemistry and response. Little wonder interest in the technology is coming from many sectors, including pharmaceutical, medical and other biotech companies.
"Chromatid paints are designed to provide a whole lot more information to a researcher than a chromosome paint," explained Tompkins. "You get orientation information, sequence and location -- so you can really see all of the possible mutations. You can discover everything all in one set of experiments."
KromaTiD's research team began its painting project with Chromosome 3. The reason was that there was already a good model system, an established cell line, and a known type of cancer associated with it. Chromosome 3 is also one of the four largest chromosomes, so it made sense from a production point of view.
"By doing Chromosome 3 first, we got almost 7 percent of the genome covered with one chromosome," Tompkins said.
Led by Dr. Andy Ray, the KromaTiD research team is currently completing work on Chromosomes 1, 2 and 4. "We'll have the four largest chromosomes all in place," Tompkins noted.
"We'll have about 30 percent of the genome covered, which is a nice number for doing screening assays - not too much, not too little," he said. "It's kind of the Goldilocks problem. If you paint the whole thing, sometimes things can get in the way of each other, so one-third tends to be just about right."
Chromosome 10 has also been completed. It has a known thyroid cancer gene on it, which is one of the company's commercial interests. In the future, KromaTiD intends to offer paint kits for all 23 chromosomes, as well as for the X and Y chromosomes.
Currently, KromaTiD is generating revenue by taking on custom projects for scientists with particular problems to solve. But that focus may soon change. Tompkins predicts KromaTiD will grow from its current five employees to 30 in the next 18 months, as it prepares to launch a kit used in the diagnosis of thyroid cancer.
It is also likely that KromaTiD will outgrow its CSU campus laboratory in the coming year. Other products are also in the queue, and Tompkins expects the company will eventually reach about 100 employees.
"Right now we're plowing ahead at a pretty steady rate," he said. "We can go a lot faster with some investment, no doubt about it. The issue with small companies is funding, so I'm out raising capital investment so we can make much faster headway."
Initial support for KromaTiD came via a Small Business Innovation Research Award from NASA, several funding arms of Colorado State University, Colorado's Office of Economic Development, and the National Institutes of Health. Recently, KromaTiD became a member of Fort Collins-based Rocky Mountain Innosphere to take advantage of its support services and funding expertise.
Cytogenetics (cell genetics) is an expanding field with myriad applications in human, animal and plant health. KromaTiD is defining itself as an innovative cytogenetics company and one to watch. For more information, visit www.kromatid.com.